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The neural mechanisms underlying the antidepressant effects of nitrous oxide remain poorly understood. This study reveals that specific activation of layer V pyramidal neurons in the cingulate cortex rescues stress-associated hypoactivity states and is driven by inhibition of calcium-sensitive potassium channels rather than NMDA-receptor antagonism.

Here, the authors show a moderate iso-orientation bias of layer 2/3 lateral connections enables functionally specific spontaneous cortical waves and optogenetic stimulation response, and modular spontaneous activity in a large-scale spiking model of primary visual cortex.

MCL1 is an anti-apoptotic protein associated with cancer and therapy resistance. Here, the authors show that MCL1 regulates mTORC1 signalling and metabolism, explaining MCL1-inhibition reported cardiotoxicity, which can be mitigated by dietary leucine supplementation.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

An integrative proteo-transcriptomic analysis reveals conserved post-transcriptional regulation mechanisms in acute myeloid leukemia and introduces POSTCODE, a tool to detect regulatory alterations in omics datasets

Tendons exhibit limited healing capacity and the role of lymphatic vessels in tendon regeneration is largely overlooked. Here they compare control and injured tendon cells from both neonatal and adult mice and identify lymphatic vessels as key regenerative niche elements.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

This study develops a barcoding method that uses machine learning models and low-coverage genome sequences for species identification across all domains of life.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Simulations show that the Solar System’s gas disk shaped how and where primitive bodies were implanted in the asteroid belt, revealing different arrival times for CM and CI parent bodies and identifying CM bodies as likely sources of Earth’s water.

By applying a magnetic field to an atomic vapour, it is shown that the large bandwidth of off-resonance slow-light media can be combined with the Faraday effect to realize a high-bandwidth dispersive probe for atomic systems. This will open up the possibility of probing atomic dynamics on a nanosecond timescale.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Superconductivity mediated by phonons is usually conventional due to isotropic electron-phonon coupling. Here, Wang et al. report highly anisotropic phonons only along [001] direction in Sr_0.1Bi₂Se₃, indicating a singular electron-phonon coupling which favors a p-wave nematic superconductivity scenario.

The analysis of essential genes in pathogens can be used to discover potential antimicrobial targets. Here, the authors use a machine learning model and chemogenomic analyses to generate genome-wide gene essentiality predictions for the fungal pathogen Candida albicans, define the function of three uncharacterized essential genes, and identify the target of a new antifungal compound.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Striatonigral neurons comprise diverse subtypes, yet their specific roles in locomotion regulation are not fully understood. Here, authors demonstrate that the Calb1+ subtype promotes locomotion, while the Kremen1+ subtype terminates ongoing movement by inhibiting the activity of Aldh1a1+ dopaminergic neurons via GABBR1 receptors.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Chronic inflammation, or ‘inflammaging’, is a key process in age-related diseases, and identification of the molecular players involved is a top priority. Cai and Han identified an evolutionary conserved functional lncRNA able to modulate the release of inflammatory SASP molecules from senescent cells through the NF-κB pathway.

A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.

In mouse models of pulmonary metastasis, adjuvant epigenetic therapy targeting myeloid-derived suppressor cells disrupts the premetastatic microenvironment after resection of primary tumours and inhibits the dissemination of residual tumour cells.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Multi-ancestry genome-wide association meta-analysis of major depression identifies new risk loci, assesses the transferability of risk loci across ancestry groups, and improves fine-mapping resolution and prioritization of candidate effector genes.

The pilot phase of PigGTEx, re-analyzing 5,457 published RNA-seq samples, presents a pan-tissue catalog of molecular quantitative trait loci. Cross-species comparisons identify traits with shared genetic regulation in humans.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Mitochondria are able to maintain two competing metabolic pathways—oxidative phosphorylation and the reductive synthesis of proline and ornithine—by generating two mitochondrial subpopulations that are enriched in either pyrroline-5-carboxylate synthase or ATP synthase.

Rare variants in the gene encoding PHGDH, the rate-limiting enzyme in de novo serine biosynthesis, are identified as responsible for serine deficiency associated with the macular degenerative disease MacTel.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Studies of samples of asteroid Ryugu returned by the Hayabusa-2 mission show that the action of water and organic material on carbonaceous asteroids lead to the widespread occurrence of micron-sized polymeric organic particles encapsulating clays and biological relevant molecules.

Most genetic studies have been done on European cohorts, which affects the efficacy of polygenic risk scores in non-European populations. Here, the authors demonstrate that a colorectal cancer PRS including Asian and European ancestries has improved performance over the European-centric PRS across racial and ethnic groups.